The evolution of the Tumor Necrosis Factor superfamily (TNFSF) in early vertebrates is inferred by comparing the TNFSF genes found in humans and nine fishes: three agnathans, two chondrichthyans, three actinopterygians and the sarcopterygian Latimeria chalumnae. By combining phylogenetic and synteny analyses, the TNFSF sequences detected are classified into five clusters of genes and 24 orthology groups. A model for their evolution since the origin of vertebrates is proposed. Fifteen TNFSF genes emerged from just three progenitors due to the whole genome duplications (WGDs) that occurred before the agnathan/gnathostome split. Later, gnathostomes not only kept most of the genes emerged in the WGDs but soon added several tandem duplicates. More recently, complex, lineage-specific patterns of duplications and losses occurred in different gnathostome lineages. In agnathan species only 7-8 TNFSF genes are detected, because this lineage soon lost six of the genes emerged in the ancestral WGDs and additional losses in both hagfishes and lampreys later occurred. The orthologs of many of these lost genes are, in mammals, ligands of death domain-containing TNFSF receptors, indicating that the extrinsic apoptotic pathway became simplified in the agnathan lineage. From the patterns of emergence of these genes, it is deduced that both the regulation of apoptosis and the control of the NF-κB pathway that depends in modern mammals on TNFSF members emerged before the ancestral vertebrate WGDs.

中文翻译：

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肿瘤坏死因子超家族：早期脊椎动物进化中的祖先功能和重塑

通过比较在人类和 9 种鱼类中发现的 TNFSF 基因来推断早期脊椎动物中肿瘤坏死因子超家族 (TNFSF) 的进化：三种无颌类、两种软骨鱼类、三种放线鱼类和肉翅目Latimeria chalumnae. 通过结合系统发育和同线性分析，检测到的 TNFSF 序列分为五个基因簇和 24 个直系同源组。提出了自脊椎动物起源以来它们的进化模型。由于在 agnathan/gnathostome 分裂之前发生的全基因组重复 (WGD)，15 个 TNFSF 基因仅​​从三个祖细胞中出现。后来，有颚体不仅保留了 WGD 中出现的大部分基因，而且很快添加了几个串联重复。最近，复杂的、特定于谱系的重复和丢失模式发生在不同的有颚类谱系中。在 agnathan 物种中，仅检测到 7-8 个 TNFSF 基因，因为该谱系很快失去了祖先 WGD 中出现的 6 个基因，后来在盲鳗和七鳃鳗中发生了额外的损失。许多这些丢失基因的直系同源物是，在哺乳动物中，含有死亡结构域的 TNFSF 受体的配体，表明外源性凋亡途径在 agnathan 谱系中变得简单。从这些基因的出现模式可以推断，现代哺乳动物中依赖于 TNFSF 成员的细胞凋亡调节和 NF-κB 通路的控制都出现在祖先脊椎动物 WGD 之前。